Real-World Data on Platinum Therapy in High-Grade Serous Ovarian Cancer Patients Progressing After PARP Inhibitor Treatment

Conference Correspondent  - ESMO 2020

It has been demonstrated that using poly (ADP-ribose) polymerase (PARP) inhibitor maintenance after platinum-based chemotherapy improves progression-free survival (PFS) and PFS to subsequent chemotherapy (second PFS or PFS2) in patients with relapsed high-grade serous ovarian cancer. However, PARP inhibitors and platinum have similar mechanisms of action, and cross-resistance has been demonstrated between the 2 therapies, resulting in some concern that there may be little benefit from subsequent platinum after PARP inhibitor progression. The authors of this research aim to provide real-world data on this topic.

Patients with high-grade serous ovarian cancer who were treated with chemotherapy after progressing on maintenance PARP inhibitors were included in the analysis. The end points examined were objective response rate (ORR), median PFS, and overall survival (OS) to subsequent platinum therapy post–PARP inhibitor treatment failure. Analyses were performed according to 3 populations based on platinum-free interval: patients who received subsequent nonplatinum chemotherapy, patients with a platinum-free interval of 6 to 12 months, and patients with a platinum-free interval >12 months.

For this study, 54 patients were included, 57.4% of which were BRCA-mutated. Of the total patient population, 7.4% received PARP inhibitors after first-line therapy, 46.3% received PARP inhibitors after second-line therapy, and 46.3% received PARP inhibitors after third (or subsequent)-line therapy. The 2 PARP inhibitors used were olaparib (63%) and niraparib (37%). Median PFS of PARP inhibitors as maintenance in the recurrent setting was 7.5 months and PFS2 was 15.4 months.

In terms of survival associated with subsequent chemotherapy after PARP inhibitors, median OS was 6.8 months for patients who received subsequent nonplatinum chemotherapy, 14.2 months for patients with a platinum-free interval of 6 to 12 months, and 28.2 months for those with a platinum-free interval >12 months. Median PFS was 5.1 months, 5.1 months, and 9.4 months for patients who received subsequent nonplatinum chemotherapy, patients with a platinum-free interval of 6 to 12 months, and those with a platinum-free interval >12 months, respectively. When excluding the 4 patients who received PARP inhibitors as first-line therapy from the assessment, survival did not change.

ORR associated with subsequent platinum therapy was 33.3%. For the patients who received subsequent nonplatinum chemotherapy, 28.6% achieved partial response, 28.6% had stable disease, and 42.9% experienced disease progression. For patients with a platinum-free interval of 6 to 12 months, 22.7% had partial response, 27.3% had stable disease, and 50.0% had progressive disease. For patients with a platinum-free interval >12 months, 20% had complete response and 25% had partial response, resulting in an ORR of 45%, whereas 50% of patients had stable disease, and 5% had progressive disease. The 4 patients who experienced complete response were BRCA-mutated patients receiving PARP inhibitors in the recurrent setting. Median PFS was 5.1 months (95% confidence interval [CI], 3.2-not applicable [NA]), 5.1 months (95% CI, 4.0-9.0), and 9.4 months (95% CI, 6.7-14.0), with a P value of .055 for the comparison in patients who received subsequent nonplatinum chemotherapy, patients with a platinum-free interval of 6 to 12 months, and those with a platinum-free interval >12 months, respectively. Median OS was 6.8 months (95% CI, 3.1-NA), 14.2 months (95% CI, 9.4-NA), and 28.2 months (95% CI, 11.9-NA), with a P value of .018 for comparison in the same patient groups.

The authors concluded that the highest and only statistically significant benefit for platinum salvage after PARP inhibitor failure in patients with high-grade serous ovarian cancer was observed for those with a platinum-free interval >12 months.

Reference

Abstract and Poster 824P. ESMO 2020. September 19-21, 2020. Real-world-data (RWD) on platinum (Pt) outcomes after PARP inhibitors (PARPi) progression in high grade serous ovarian cancer (HGSOC) patients (p).

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Last modified: September 23, 2020